Structure and Neuroprotector Properties of a Complex Compound of Lithium with Comenic Acid

Int J Mol Sci. 2023 Dec 24;25(1):286. doi: 10.3390/ijms25010286.

Abstract

The structure, antioxidant and neuroprotective properties of lithium comenate (lithium 5-hydroxy-4-oxo-4H-pyran-2-carboxylate) were studied. Lithium comenate was obtained by reacting comenic acid (H2Com) with lithium hydroxide in an aqueous solution. The structure of lithium comenate was confirmed via thermal analysis, mass spectrometry, IR, NMR and UV spectroscopy. The crystal structure was studied in detail via X-ray diffraction. The compound crystallized in a non-centrosymmetric space group of symmetry of the orthorhombic system Pna21 in the form of a hydrate, with three water molecules entering the first coordination sphere of the cation Li+ and one molecule forming a second environment through non-valent contacts. The gross formula of the complex compound was established [Li(HCom)(H2O)3]·H2O. It has been established that lithium comenate has a pronounced neuroprotective activity under the excitotoxic effect of glutamate, increasing the survival rate of cultured rat cerebellar neurons more than two-fold. It has also been found that the pre-stress use of lithium comenate at doses of 1 and 2 mg/kg has an antioxidant effect, which is manifested in a decrease in oxidative damage to the brain tissues of mice subjected to immobilization stress. Based on the data available in the literature, we believe that the high neuroprotective and antioxidant efficacy of lithium comenate is a consequence of the mutual potentiation of the pharmacological effects of lithium and comenic acid.

Keywords: antioxidant; comenic acid; excitotoxicity; gamma-pyrones; lithium; lithium comenate; lithium complex compounds; neuroprotection.

MeSH terms

  • Animals
  • Antioxidants* / pharmacology
  • Carboxylic Acids*
  • Glutamic Acid
  • Lithium* / pharmacology
  • Mice
  • Pyrones*
  • Radioisotopes*
  • Rats
  • Water

Substances

  • Lithium-4
  • Lithium
  • comenic acid
  • Antioxidants
  • Glutamic Acid
  • Water
  • Radioisotopes
  • Carboxylic Acids
  • Pyrones